title: West syndrome, microcephaly, grey matter heterotopia and hypoplasia of corpus callosum due to a novel ARFGEF2 mutation.
abstract: West syndrome (WS) is an epileptic encephalopathy of childhood, defined by the presence of clustered spasms usually occurring before the age of 1 year, hypsarrhythmia on EEG that is notoriously difficult to define, and developmental arrest or regression. The incidence of WS is 1:3200 live births with an aetiology-dependent prognosis. Up to 80% of children with symptomatic WS suffer from mental retardation, and approximately 50% develop Lennox-Gastaut syndrome. Using homozygosity mapping followed by exome sequencing, we identified a ADP-ribosylation factor (ARF) guanine nucleotide-exchange factor two (brefeldin A-inhibited) (ARFGEF2) mutation in five related infants with WS. ARFGEF2 is involved in the activation of ARFs by accelerating replacement of bound guanosine diphosphate (GDP) with Guanosine triphosphate (GTP), and is involved in Golgi transport. A mutation in ARFGEF2 has been previously described only once, causing microcephaly and periventricular heterotopia. Here, we describe a novel ARFGEF2 mutation in five related patients presenting with WS, microcephaly, periventricular heterotopia and thin corpus callosum.
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Banne
authors.forename: Osama
authors.initials: O
authors.lastname: Atawneh
authors.forename: Marco
authors.initials: M
authors.lastname: Henneke
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
authors.forename: Simon
authors.initials: S
authors.lastname: Edvardson
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000473:pathology; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008831:Microcephaly / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D011859:Radiography; D013036:Spasms, Infantile / Q000235:genetics* / Q000473:pathology*
chemical_list: C119088:ARFGEF2 protein, human; D020662:Guanine Nucleotide Exchange Factors
keywords: Epilepsy and seizures; Genetics; Neurosciences